2016 Fiscal Year Final Research Report
PPARgamma-targeting Nanomedicine for the Treatment of Atherosclerotic Plaque Rupture
Project/Area Number |
15K19384
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Cardiovascular medicine
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Research Institution | Kyushu University |
Principal Investigator |
Junchiro Koga 九州大学, 循環器病未来医療研究センター, 学術研究員 (10746142)
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Keywords | 分子血管学 / 動脈硬化 / ナノメディスン |
Outline of Final Research Achievements |
Objective―Inflammatory monocytes/macrophages produce various proteinases and induce rupture of atherosclerotic plaques. We have tested a hypothesis that nanoparticle-mediated delivery of peroxisome proliferator-activated receptor-γ agonist pioglitazone to monocytes/macrophages inhibits plaque ruptures. Approach and Results―Poly(lactic-co-glycolic-acid) nanoparticles (NPs) were prepared for targeting delivery to monocytes/macrophages. Weekly intravenous administration of pioglitazone-NPs decreased buried fibrous caps, suggesting healed ruptures, in the brachiocephalic arteries of Apoe-/- mice with a high-fat diet and angiotensin II infusion. Pioglitazone-NPs also inhibited the activity of proteases and decreased expression of inflammatory cytokines in macrophages. Conclusions―Nanoparticle-mediated delivery of pioglitazone inhibited macrophage activation and plaque ruptures in ApoE-/- mice. These results demonstrate a promising strategy to prevent atherosclerotic plaque ruptures.
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Free Research Field |
循環器内科学
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